Null mutation of copper/zinc superoxide dismutase in Drosophila confers hypersensitivity to paraquat and reduced longevity.

Abstract

The role of copper/zinc-containing superoxide dismutase (cSOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) in metabolic defense against 02 toxicity in Drosophila is examined through the properties of a mutant strain carrying a cSOD-null mutation, cSOD1'08. Homozygotes are viable as larvae, which indicates that cSOD is not essential for cell viability per se. cSOD"'0 confers recessive sensitivity to the superoxide anion (O )-generator paraquat and to the transition metal compound CuS04, which indicates that the cSOD-nufl condition in fact leads to impaired°2 metabolism.The primary biological consequences of the reduced°2 dismutation capacity of cSOD"IY Drosophila are realized in the adult as infertility and reduction in life-span. We conclude that the infertility and reduced life-span of cSODR"'O adults arise as a consequence of the reduced capacity of embryos, larvae, and pupae to adequately protect developing preimaginal cells from 02-jnitiated cytotoxic damage.

Phenotypic effects of familial amyotrophic lateral sclerosis mutant Sod alleles in transgenic Drosophila

“…1 and 2). The (SodϪ); Sod x16/x39 flies had no detectable SOD activity and, in two replicate experiments, their life spans were decreased by 77% and 88% in comparison with the dSod; Sod x16/x39 mean, consistent with the findings of other investigators (23).…”

Oxidative stress, aging and longevity in Drosophila melanogaster

“…2 ) than controls [19]. A partial Cu/Zn SOD null mutant (3.5% of the SOD activity of the control line) had a similar longevity to controls but a higher sensitivity to paraquat [20].…”

High-quality life extension by the enzyme peptide methionine sulfoxide reductase

“…In the fruit fly Drosophila, the oxidized protein content also increases with age (4), and those animals with longer lifespans have greater resistance to ROS (5)(6)(7)(8). Overexpression of superoxide dismutase and catalase, two enzymatic components in the cellular antioxidant system, together increases the lifespan of Drosophila (9)(10)(11)(12), whereas genetic disruption of the superoxide dismutase͞catalase antioxidant system in Drosophila shortens its lifespan (13,14). Other interventions to extend lifespan such as caloric reduction and manipulations of genes involved in cell metabolism and growth-factor signaling cascades may work indirectly by decreasing the ROS production or increasing the level of antioxidants (2,10).…”